Genetic Patterns in Europe and the Surrounding Regions.

摘要

Individuals of European descent make up a significant portion of the world's population and are one of the four main branches of the human population tree (the remaining three are Africans, East Asians, and Native Americans). Because of this, it is important to understand the evolution of European populations. A further understanding of European evolutionary history will help us better understand human biology and lay the ground work for future research including those involving Genome Wide Association Studies, by helping to identify issues such as population stratification between cases and controls, as well as the move toward individual medicine. A better understanding of European genetic history will also complement the research in other fields of European study such as anthropology, archeology, and history. In this thesis, I will explore European evolution on a genome-wide level as well as at the individual gene/gene region level.;The first part of this thesis will explore Europe on a genome-wide level. In this section I use STRUCTURE, principle components analysis, and least-square population trees to determine the population structure among several European populations and to determine if the population structure best fit into the demic diffusion model, which says most modem Europeans are descendants of Neolithic settlers, or the cultural diffusion model, which argues that most modern Europeans are descendants of the original Paleolithic settlers. These analyses were done using two large datasets. The first is composed of 506 haplotypes and the second is composed of 320 high Fst SNPs. Both data sets show a general pattern starting in Southwest Asia and moving into Southern Europe, through Northwest Europe and finally ending in Eastern Europe, which best fits with the expectations of the demic diffusion model. These populations tend to form four tightly clustered groups: Southwest Asians, Southern Europeans, Northwestern Europeans, and Eastern Europeans.;The second section and majority of this thesis will look at several gene regions where one or multiple SNPs, haplotypes, or other variants show European specific patterns and may have an effect on or show association with a phenotype. These regions include a ∼900 kb inversion at 17q21, blue-eye associated alleles at OCA2, light skin pigmentation alleles at SLC24A5 and SLC45A2, a European specific haplotype at MC1R, a light pigmentation allele at IRF4, a European specific haplotype at DRD2, and European specific alleles at LCT including one associated with lactase persistence. At all these regions, I looked at the frequency distribution of all alleles of interest, at LD across the region and looked for evidence of selection using LRH tests. I found evidence of selection at OCA2, SLC24A5, IRF4, and LCT in Europeans. I also saw evidence of selection at SLC24A5 in East Africans, Southwest Asians, and Central Asians, and at new alleles at OCA2 in East Asians, at SLC45A2 in East Asians and Native Americans, and at LCT in Africans. At 17q21, I also estimated the age of the most recent common ancestor of the inversion (13,600 to 108,400) using STRPs and confirmed the orientation of the H2 (inversion) haplotype using fluorescent in situ hybridization (FISH)